Dental caries is one of the most common diseases of childhood. It occurs in children of all socioeconomic classes and in every country around the world. In the United States, there is disparity in caries prevalence such that 80% of the caries occur in 20% of the children, primarily minority children or those from low income families. Although there is clear evidence that dental caries is a multifactorial infectious disease with many environmental contributory factors, there is also strong evidence for a host genetic component in the etiology of this disease. Currently, the most reliable predictor of a child's future risk for caries is the presence of one or more carious teeth. Other environmental factors contribute to this risk but do not provide the level of specificity needed for the targeting of effective preventive measures. The objective of this application is to screen candidate genes to identify sequence polymorphisms that occur more frequently in subjects with dental caries than in those without caries. A secondary objective is to initiate the collection of families with multiple affected children to be used for a genome scan in a future application. The central hypothesis of the application is that sequence variations in one or more candidate genes, combined with environmental factors, can be used to predict caries risk prior to the occurrence of disease. Two hundred affected children aged 3 to 4 years and age and race matched controls will be ascertained from Iowa for linkage disequilibrium studies. Families with multiple affected siblings will be ascertained whenever possible. Candidate genes will include genes involved in enamel mineralization and in salivary buffering. Collection of families will be done to facilitate future genome wide scans for caries susceptibility loci. Identification of genetic markers for dental caries will provide us with a better understanding of the caries process on an individual basis, a more reliable method to assess caries risk and will facilitate the development of targeted preventive strategies.